Method and apparatus for the treatment of cancer

ABSTRACT

A method and apparatus for therapeutically treating cancer is provided. The apparatus includes a magnetic field generator for producing a controlled, fluctuating, directionally oriented magnetic field parallel to a predetermined axis projecting through a malignant neoplasm. In one aspect, a field detector measures the magnetic flux density along the predetermined axis. The applied magnetic field may comprise a full-wave rectified signal oscillated at predetermined frequencies to maintain a preselected ratio of frequency to the effective flux density, where the ratio regulates the growth characteristics of cancer cells of the neoplasm. This ratio is maintained by adjusting the frequency of the fluctuating magnetic field and/or by adjusting the intensity of the applied magnetic field after nulling out the local magnetic field at that region containing the neoplasm. In one aspect, a synergistic therapeutic cancer treatment is obtained by exposing cancer cells to the magnetic fields of the invention in the presence of a chemotherapeutic cancer agent.

This is a continuation of application Ser. No. 08/003,787 filed on Jan.13, 1993, now abandoned which is a continuation of Ser. No. 07/902,929filed on Jun. 23, 1992, now U.S. Pat. No. 5,183,456 which is acontinuation application of Ser. No. 703,383 filed May 21, 1991, nowU.S. Pat. No. 5,211,622 which is a continuation application of Ser. No.437,485 filed Nov. 15, 1989, now U.S. Pat. No. 5,045,050.

TECHNICAL FIELD

The present invention relates generally to the treatment of cancer. Morespecifically, it provides in one aspect a method and apparatus by whicha reduction in the proliferation rate of cancer cells is achievedthrough the use of fluctuating magnetic fields which are tuned topreselected frequencies. In the presence of a chemotherapeutic agent,target cancer cells are exposed to the therapeutic fields, producing areduction in the proliferation of cancer cells greater than that of thechemotherapeutic agent alone. In another aspect, the present inventionreduces malignancy by potentiating differentiation of the cells.

BACKGROUND OF THE INVENTION

Approximately one-fifth of all deaths in the United States are caused bycancer. An estimated $20 billion is spent annually in the United Statesin connection with the care and treatment of cancer patients. Althoughvast sums are spent on cancer research worldwide, little is known aboutthe initiation and progression of this disease.

As will be appreciated by those skilled in the art, cancer cells arerelatively autonomous in that they fail to respond to normal biologicalsignals that control cellular growth and metabolism in the livingorganism. Malignant tumors are characterized by their ability tometastasize. In metastasis, cancer cells spread through the organismproducing tumors at sites remote from the point of origin. It isgenerally accepted that the number of cell membrane processes isinversely proportional to the probability of cell metastasis. Malignantneoplasms are generally classified as those arising from supportivetissues such as connective tissue, bone, cartilage or striated muscle(sarcomas) and those arising from epithelial tissue (carcinomas). Inanother type of cancer known as "leukemia," cancer cells circulatepredominantly in the bloodstream. In general, leukemias originate in thelympatic tissues and bone marrow where blood components are formed.After a neoplasm develops in an organism, it may progress from a benignform to a malignant form or from a low-level malignancy to a rapidlyproliferating malignancy. Although millions of cells may metastasizefrom a primary tumor, it is known that only a few of these cellsactually result in metastatic lesions at other sites.

While the behavior of cancer cells is unpredictable, it is generallyacknowledged that early recognition of cancer is paramount to successfultreatment. The most common modern-day method of treating cancer issurgical intervention. Both primary tumors and metastatic tumors may besurgically removed. It is also known that malignant tumors, particularlylymphomas, leukemias and carcinomas can be treated by radiation therapy,for example by exposure to gamma rays and the like. More recently,advances have been made in the use of chemotherapeutic agents, often inconjunction with surgical and/or radiation treatment. It will beappreciated by those skilled in the art that rapidly progressing cancershave a high percentage of cells undergoing mitosis, i.e. a large growthfraction, and it is these cancers that are particularly susceptible tochemotherapy. More recently, immunotherapeutic techniques which utilizeantibodies to which cytocidal agents are linked have met with limitedsuccess. However, the need for a more effective treatment for cancer isclearly evidenced by the large number of cancer deaths worldwide.

In U.S. Pat. No. 4,622,952, entitled "Cancer Treatment Method," a methodof cancer treatment is described by which the application of externalelectromagnetic energy allegedly achieves biophysical alterationsincluding thermal changes, the stimulation of intracellular interferonproduction and the stimulation of intracellular prostaglandinproduction. The process includes the step of empirically tuning externalelectromagnetic energy to a "resonant" frequency which achieves aprecise increment of heat rise within the cancer cell and whichstimulates the intracellular production of interferon and/orprostaglandins. The present invention utilizes a group of resonantfrequencies, not derived from heating consideration, but derived insteadfrom a basic formula that acts to selectively control the transport ofvarious electrolyte ions into and out of cancer cells, in a mannerresulting in substantially no measurable temperature increase within thecells.

In recent years, multi-disciplinary investigations of physiologicalprocesses have provided evidence suggesting that electric and magneticfields play an important role in cell and tissue behavior. In U.S. Pat.No. 4,818,697, entitled "Techniques for Enhancing the Permeability ofIons Through Membranes," which has been assigned to the assignee of thepresent invention and the disclosure of which is incorporated herein byreference, a method and apparatus are disclosed by which transmembranemovement of a preselected ion is magnetically regulated using atime-varying magnetic field. The fluctuating magnetic field ispreferably tuned to the cyclotron resonance energy absorption frequencyof the preselected ion. This important discovery brought to light theinterplay of local magnetic fields and frequency dependence in iontransport mechanisms.

In U.S. patent application Ser. No. 172,268, filed Mar. 23, 1988, thedisclosure of which is incorporated herein by reference, the inventorsof the present invention disclose that cyclotron resonance can be usedto control tissue development. In U.S. patent application Ser. No.254,438, entitled "Method and Apparatus for Controlling the Growth ofNon-Osseous, Non-Cartilaginous, Solid Connective Tissue," filed Oct. 6,1988, the disclosure of which is incorporated herein by reference, thepresent inventors disclose a method of controlling the growth ofnon-osseous, non-cartilaginous connective tissue which utilizescyclotron resonance frequencies. In U.S. patent application Ser. No.295,164, entitled "Techniques for Controlling Osteoporosis UsingNon-Invasive Magnetic Fields," filed Jan. 9, 1989, the disclosure ofwhich is incorporated herein by reference, the present inventorsdisclose a method of controlling osteoporosis using cyclotron resonancemagnetic fields. In U.S. patent application Ser. No. 343,017, filed Apr.25, 1989, entitled "Methods and Apparatus for Regulating TransmembraneIon Movement Utilizing Selective Harmonic Frequencies and SimultaneousMultiple Ion Regulation," the disclosure of which is incorporated hereinby reference, the present inventors disclose a method of utilizingtherapeutic higher-harmonic frequencies and a method of simultaneouslycontrolling the transport of multiple ions. In U.S. patent applicationSer. No. 395,247, filed Aug. 17, 1989, entitled "Treatment for StrokeVictims," the present inventors describe a method and apparatus formagnetically treating stroke victims.

The present invention discloses a new and unique apparatus fornon-invasive treatment of cancer which is directed at reducing the rateof growth of neoplasms through the action of a fluctuating magneticfield.

SUMMARY OF THE INVENTION

In one aspect, the present invention provides an apparatus fordecreasing the proliferation rate of cancer cells in the presence of achemotherapeutic agent. That is, the conventional reduction in thenumber of cancer cells produced by exposing the cells to achemotherapeutic agent is enhanced by the magnetic fields of the presentinvention. The inventive apparatus includes means for generating anapplied magnetic flux parallel to a predetermined axis and projectingthrough a predetermined space. The predetermined space is occupied bycancer cells or a tumor present in a living subject, preferably eitherman or animal, in the presence of a chemotherapeutic agent. It shouldalso be noted that the present invention may also be useful in thetreatment of plant tumors. Means for measuring total magnetic fluxdensity parallel to the predetermined axis extending through thepredetermined space is provided so that the magnetic flux density alongthe axis can be monitored. Means in association with the flux generatingmeans is provided so that the applied magnetic flux can be oscillated.Finally, means for creating and maintaining a relationship between therate of fluctuation of the magnetic flux and the intensity of themagnetic flux density is provided, where the predetermined relationshipdecreases the proliferation rate of the target cancer cells. In anotheraspect, this predetermined relationship is such that the number of cellmembrane processes is increased to decrease metastatic potential.

In one embodiment, the means for applying a magnetic flux includes twoopposed field coils arranged in Helmholtz configuration such that anapplied magnetic field having known parameters along the predeterminedaxis can be generated between the coils. In another embodiment, a secondpair of field coils are placed such that they generate an appliedmagnetic flux along an axis perpendicular to the predetermined axisdefined by the first coil pair. In this same manner, a third pair ofopposed coils can be utilized such that magnetic fields are applied bythe three coil pairs along the x, y, z axes of a Cartesian coordinatesystem. The second and third coil pairs are similarly actuated toprovide a predetermined relationship between the frequency of themagnetic flux and the intensity of the magnetic flux density.

In another aspect, a method for decreasing the proliferation of cancercells is provided utilizing the apparatus of the present invention.Therein, a tumor comprising cancer cells in the presence of achemotherapeutic agent in a living subject, either man or animal, ispositioned adjacent to the magnetic field generating means. A specificmagnetic flux extending through the space in which the target cancercells are positioned is generated parallel to a predetermined axisprojecting through the cells. A relationship is then created between thefrequency of the oscillating magnetic flux and the intensity of themagnetic flux density where the relationship decreases the proliferationrate of the target cancer cells, i. e. the number of cancer cellsexisting after a predetermined period is less than that withchemotherapy alone. In a preferred embodiment of the present invention,the magnetic flux generating means comprises a pair of field coils aspreviously described. Also, in a preferred embodiment of the invention,the predetermined therapeutic relationship between the frequency of themagnetic flux permeating the cancer cells and the intensity of themagnetic flux is determined by the cyclotron resonance equation f_(c)/B=q/(2πm), where f_(c) is the frequency in Hertz, B is the averagevalue of the magnetic flux density in Tesla parallel to thepredetermined axis, q/m has a value of from about 5×10⁵ to about 100×10⁶Coulombs per kilogram and where B has a value of less than about 1×10⁻²Tesla. In a particularly preferred embodiment, q/m is the charge-to-massratio of a preselected ion present in the cancer cells.

In still another aspect, a system for decreasing the proliferation ofcancer cells is provided which includes means for generating an appliedmagnetic flux parallel to a predetermined axis and projecting through apredetermined space where the space is occupied by cancer cells of aliving subject in the presence of a chemotherapeutic agent. In thisparticular configuration, the magnetic flux generating means includes atleast two opposed field coils having an axis extending through andparallel to the predetermined axis projecting through the predeterminedspace. Each of the field coils has at least two windings. One winding isdesignated an ac winding and the other is designated a dc winding. Meansin association with the coils is provided for supplying a direct currentto the dc winding and an alternating current to the ac winding. Meansfor measuring the ambient or local field existing in the predeterminedspace in the region of the cancer cells is also provided. Means inassociation with the flux generating means for controlling the directcurrent to the dc windings is supplied such that the dc windings may beactivated to create a magnetic flux which reduces the ambient magneticflux to substantially zero. A full-wave rectifier circuit and anoscillator are provided in association with the ac windings and thecurrent supply means in order to produce an ac magnetic field componentalong the predetermined axis in the predetermined space which has apreselected rms value, where the rms value decreases the proliferationof cancer cells. In addition, the system may use a sinusoidal signal tothe ac windings, offset by a constant bias current equal to therms-value utilized when full-wave rectification is used.

The system may further include a second pair of opposed field coilswhich define an axis extending through the region of the cancer cellswhich is perpendicular to the predetermined axis defined by the firstcoil pair. Further, a third coil pair can be provided such that theambient field along the x, y, z axes of a Cartesian coordinate system isreduced to zero, with an applied field having the therapeutic non-zeroaverage value as provided by the present invention being generated alongeach of the axes.

With respect to the aforementioned system which includes ac windings anddc windings, there is provided by the present invention a method fordecreasing the proliferation of cancer cells which comprises the stepsof generating an applied magnetic flux parallel to a predetermined axiswhich projects through a predetermined space, with the space beingoccupied by cancer cells in a living subject in the presence of achemotherapeutic agent. The ambient field along the predetermined axisin the predetermined space is measured using a magnetic field sensorwhich is capable of measuring both static and time-varying magneticfields. Utilizing the dc windings and a power supply, a magnetic flux isgenerated which reduces the ambient field to substantially zero alongthe axis. The ac windings are then used to generate an ac magnetic fieldhaving a component along the predetermined axis which has a non-zeroaverage value that is effective in decreasing the proliferation rate ofcancer cells.

In still another aspect, the present invention provides a method for thetherapeutic treatment of cancer in which the proliferation rate ofcancer cells is reduced by the fluctuating magnetic fields provided bythe present invention without the concurrent application of achemotherapeutic agent.

Still further, treatment in accordance with the present invention is inone embodiment effective in stimulating the differentiation of cellprocesses, i.e., neurites to decrease the metastatic potential of thecells.

The aforementioned control of cancer cell growth is also achieved tovarying extents in one embodiment of the present invention through theuse of higher-harmonic tuning and multiple ion tuning is also provided.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 diagrammatically illustrates one preferred placement of theapparatus of the present invention.

FIG. 2 is a front elevational view of the treatment heads of the presentinvention in one embodiment.

FIG. 3 is a graph which illustrates the magnetic flux density value (B)in the present invention.

FIG. 4 is a block diagram of the functional elements of a preferredcircuit for use in the present invention.

FIG. 5 is a side elevational view in which the present invention isshown utilizing three pairs of coils.

FIG. 6 is a perspective view of the present invention for use insystemic treatment of cancer.

FIG. 7 is a block diagram of the circuitry of one embodiment of thepresent invention for use in systemic treatment.

DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION

Referring now to FIG. 1 of the drawings, cancer treatment apparatus 20is shown in position on a subject's leg 22. It is to be understood thatboth the apparatus and the method of the present invention are suitablefor use in decreasing the proliferation rate of cancer cells in bothanimal and human subjects. As used herein, the term "cancer" shall haveits customary meaning, although it is to be noted that the presentinvention may be useful in the treatment of non-cancerous neoplasms aswell as cancerous neoplasms. The term "decreasing the proliferation" and"decreasing the proliferation rate" shall mean that the number of cancercells existing after a predetermined period of treatment in accordancewith the present invention is less per unit volume than the number ofcancer cells in a control without treatment in accordance with thepresent invention. The term "chemotherapeutic agent" shall mean one ormore of the various anti-cancer treatment drugs, the identity and natureof which will be known by those of skill in the art. It is known thatmany of these agents produce a decrease in cancer cell proliferationrates. Thus, the target tissue which is to be affected is a region ofcancer cells such as a malignant tumor. Although the present inventionhas been shown to be useful in decreasing the proliferation rate ofneuroblastoma tumor cells in the presence of a chemotherapeutic agent,it is believed that the present invention will be effective in thetreatment of other cancer cells, including carcinoma, leukemia, sarcoma,lymphoma, melanoma, myeloma and the like.

A malignant neoplasm 24, shown here as a sarcoma in the subject's thigh,is positioned in a predetermined volume 26 between treatment heads 28and 30 of cancer treatment apparatus 20. It is within this predeterminedspace or volume that the therapeutic oscillating magnetic field isgenerated. Hence, as will be appreciated, there exist within space 26cancer cells which are multiplying by mitotic division in theuncontrolled manner characteristic of cancers. As with all cancertreatments, it is preferred that treatment be commenced immediatelyfollowing detection of the condition. In this embodiment of theinvention, a chemotherapeutic agent, for example cytosine arabinoside,is administered to the subject in the customary manner. The dosage willbe consistent with the known effective dosage for the particularchemotherapeutic agent, although it is anticipated that a reduction inthe standard dosage may be facilitated by the present invention.Accordingly, a cancer chemotherapeutic agent is administered to thepatient either systemically or locally, for example through the use ofcancer cell-specific antibodies to which chemotherapeutic agents areconjugated. The most preferred chemotherapeutic agents which aresuitable in the practice of the present invention are those whichdemonstrate substantially enhanced therapeutic action in the treatmentof cancer when administered in connection with selected frequencies ofcyclotron resonance tuning as provided by the present invention overcontrol applications of the chemotherapeutic agent without exposure tothe magnetic fields of the present invention. This can be readilydetermined by in vitro or in vivo animal experiments. Preferredchemotherapeutic agents believed to be useful in this respect includealkylating agents and nucleic acid analogs.

In order to better appreciate the configuration of treatment heads 28and 30 as provided by the present invention, reference is now made toFIG. 2 of the drawings in which treatment heads 28 and 30 are shown asincluding housings 32 and 34 of a non-magnetic material such as plastic.Each housing 32, 34 encloses a field coil 36 and 38. At least one of thetreatment heads encloses a magnetic field sensing device 40, such as aHall-effect device, shown in FIG. 2 enclosed within housing 32 oftreatment head 28. The power source for driving the field coils ispreferably external, but may be a battery or the like shown as powersource 42 in treatment head 30. Straps 44 and 46 are provided by whichcancer treatment apparatus can be conveniently attached to the patient.

While field coils 36 and 38 are the preferred means by which an appliedmagnetic field is generated in the present invention, those skilled inthe art will appreciate that other electromagnets or possibly permanentmagnets may be adapted for use in the present invention, and any suchuse is intended to come within the scope of the present invention. Also,the radius of each field coil 36 and 38, as well as the turns of thewindings, may vary in accordance with the principles of the presentinvention. In the most preferred arrangement, the geometry and relativeposition of treatment heads 28 and 30 during treatment are such thatfield coils 36 and 38 operate as Helmholtz coils. Hence, those skilledin the art will recognize that in the most preferred arrangement, fieldcoils 36 and 38 are substantially identical, field-aiding, parallelcoaxial coils separated by a distance equal to the radius of each coil.

It will be appreciated that the malignant neoplasm to be affected willgenerally be subject to local magnetic influences. As used herein, theterm "local magnetic field," "ambient magnetic field" or the like shallbe defined as the magnetic influences, including the earth's magneticfield or geomagnetic field, which create a local magnetic flux thatflows through the target tissue. "Magnetic flux density" shall bedefined in the customary manner as the number of magnetic field linesper unit area through a section perpendicular to the direction of flux.Factors contributing to the local magnetic field in addition to thegeomagnetic field may include localized regions of ferromagneticmaterials or the like. In one embodiment of the present invention, fieldcoils 36 and 38 are used to create an applied, fluctuating magneticfield which, when combined with the local magnetic field parallel to apredetermined axis extending longitudinally between treatment heads 28and 30, produces a combined magnetic field or composite field having acomponent along the axis which has a precisely controlled, predeterminedratio of frequency to average magnetic flux density.

In one embodiment, and referring again to FIG. 2 of the drawings, thisrelationship is created using microprocessor 48 which is incommunication with electronics necessary to control the oscillation andintensity of the magnetic flux which permeates the target cells. Also,leads 50 and 52 are shown by which the various components of cancertreatment apparatus 20 are interconnected, along with other such leadswhich are not shown. Magnetic sensor or magnetometer 40 measures thetotal or composite magnetic flux which passes through the predeterminedspace between treatment heads 28 and 30 thus providing an accuratemeasurement of the magnetic field which permeates the malignant neoplasm24. Predetermined axis 54 is shown in FIG. 1 as extending betweentreatment heads 28 and 30. It will be appreciated that the applied fieldgenerated using treatment heads 28 and 30 may be in either direction ofpredetermined axis 54 and that the local or ambient magnetic field willalso have a component along axis 54 which either augments or decreasesthe applied magnetic flux. The relatively low applied flux density inthe precise, predetermined relationships of combined flux density andfrequency provided by the present invention are to be maintained duringtreatment, notwithstanding the influence of the local magnetic field.This may be achieved in essentially two preferred manners which will beexplained more fully herein. Thus, magnetic field sensor 40 is providedto determine the level of the magnetic flux density of the localmagnetic field.

The unexpected and superior results of the present invention areachieved by creating a fluctuating magnetic field having a magnetic fluxdensity parallel to predetermined axis 54, with the magnetic fluxdensity along axis 54 being maintained at a predetermined ratio of thefrequency of the fluctuations to the non-zero value of the magnetic fluxdensity. In this embodiment, the magnetic flux density parallel topredetermined axis 54 has a non-zero time-average value. Morespecifically, as illustrated in FIG. 3 of the drawings, the therapeuticmagnetic field of the present invention can be thought of as a staticfield having reference level A on which a fluctuating magnetic field issuperimposed. It comprises a time-varying component which varies inamplitude but not direction and a steady reference value around whichthe time-varying component varies. Reference level A is the non-zeroaverage value of the flux density (B). Therefore, it will be understoodthat the non-zero time-average, or net average value where the magneticfield is the combination of the local field and the applied field, alongpredetermined axis 54 is utilized since the magnitude B of the compositeflux density changes at a predetermined rate due to oscillation orfluctuation of the applied magnetic flux. Thus, an average value isutilized which is a non-zero average value illustrated at point (c).This reflects that although the magnetic flux density along the axis isoscillating at a controlled rate, the field is regulated to ensure thatthe field is always unipolar; that is, the field is always in the samedirection along predetermined axis 54.

As stated, it has been found that rather precise relationships of theflux density of the magnetic field to the frequency of the fluctuationsare used in the present invention to provide therapeutic results. Theseratios of frequency to composite flux density are found in accordancewith the following equation:

    f.sub.c /B=q/(2πm)

where f_(c) is the frequency of the combined magnetic field in Hertz, Bis the net average value of the magnetic flux density of the magneticfield (the combined field where a local field component is present)parallel to predetermined axis 54 in Tesla and q/m has a value of fromabout 5×10⁵ to about 100×10⁶ Coulombs per kilogram. B preferably has avalue not in excess of about 1×10⁻² Tesla. In order to increase theinhibition of cancer cells in the presence of a chemotherapeutic agent,the following frequency and associated combined magnetic flux density(B) are preferred: ##EQU1## at an ac amplitude, peak-to-peak of 40microTesla.

In use, malignant neoplasm 24 in the presence of a chemotherapeuticagent is then subjected to a fluctuating magnetic field as describedherein for a period of time effective to inhibit the rate of growth ofthe neoplasm by decreasing the proliferation rate of cancer cells. Whilethe length of time necessary for successful treatment may vary, it isanticipated that up to about 100 days of treatment will providebeneficial results. Longer treatment may be desirable in certainapplications.

In another embodiment of the present invention, values for q and m aredetermined with reference to a preselected ionic species. It will beknown by those skilled in the art that the biochemical milieu of amalignant neoplasm comprises a mixture of various ions in theintracellular and intercellular fluids. These ions include potassiumions, magnesium ions, sodium ions, chloride ions, phosphate ions,sulfate ions, carbonate ions, bicarbonate ions and the like and variousions formed by the dissociation of amino acids, proteins, sugars,nucleotides and enzymes. By utilizing the values of charge and mass fora preselected ion in the equation set forth above, which will berecognized by those skilled in the art as the cyclotron resonancerelationship solved for f_(c) /B, ratios of frequency to magnetic fluxdensity can be determined which will therapeutically reduce the rate ofgrowth of malignant neoplasm 24 in accordance with the presentinvention. By using the charge-to-mass ratio of a preselected ion, aspecific cyclotron resonance frequency for the ion can be determined. Bythen tuning cancer treatment apparatus 20 to maintain a combinedmagnetic flux density having the proper cyclotron resonance frequency,the neoplastic tissue containing the preselected ion can be treated tobring about the desired decrease in the proliferation rate of the cancercells. More specifically, in a preferred embodiment of the invention, bytuning to Ca⁺⁺ or K⁺ it is believed that progression of a tumor in thepresence of serum lacking fetal growth factors can be slowed inaccordance with the present invention.

Hence, it will be appreciated by those skilled in the art that in thepresent invention, by synergistically enhancing the effects ofchemotherapeutic agents in the treatment of cancer, it may be possibleto reduce the quantity of or the time course of the chemotherapeuticagents administered to the patient, resulting in a decrease indose-related side effects.

It will also now be appreciated by the prior explanation of preferredembodiments of the present invention and from the equation forestablishing a cyclotron resonance relationship, that either thefrequency of the fluctuating magnetic field or the magnitude orintensity of the magnetic flux density along the predetermined axis, orboth the frequency and the intensity of the flux density, can beadjusted to provide a magnetic field which has the desiredcharacteristics. However, it is preferred to maintain a constantfrequency which thus requires that the intensity of the applied magneticflux density be adjusted to compensate for changes in the local magneticfield in order to maintain a constant ratio of frequency to magneticflux density. For example, if it is necessary to maintain a frequency of16 Hz and an average flux density of 4.07×10⁻⁵ Tesla for K⁺, changes inthe local field which would otherwise cause unwanted deviations in thecombined magnetic flux density must be corrected by increasing ordecreasing the applied magnetic flux density accordingly. This is mostpreferably performed by the microprocessor in connection with both thefield generating means and the field-sensing device. Alternatively, ifchanges in the combined magnetic flux density occur due to changes inthe local magnetic field, the frequency of the oscillations can then bechanged so that the preferred ratio is maintained. Once again, it isimportant to realize that the value of B is the average compositemagnetic flux density parallel to the predetermined axis since themagnitude of the flux density changes as the field is oscillated. Itwill be understood that detection of changes in the magnetic field dueto changes in the ambient component should be at intervals frequentenough to provide a frequency-to-magnetic field ratio which issubstantially constant, notwithstanding the changes in the local fieldcomponent.

Referring again to FIGS. 1 and 2 of the drawings, each field coil 36, 38preferably has up to about 3000 turns or loops of conducting wire, thediameter d of each loop being preferably up to about 300 centimeters.The number of turns of wire N, the diameter of the coils, the separationof the coils, and the wire gauge are critical only insofar asconventional practice requires constraints on these and other designparameters to allow optical performance characteristics in achievingpredetermined flux densities as required in the preferred practice ofthe present invention. As stated, other magnetic field generating meansmay be suitable for use in the present invention and are contemplated asfalling within the scope of this invention.

It is also to be understood that the applied magnetic field whichresults in a combined magnetic flux density along predetermined axis 54may be produced by a sinusoidal signal or from a full-wave rectifiedsignal applied to field coils 36, 38. It may also be appropriate in someinstances to reduce components of the local magnetic field which are notparallel to predetermined axis 54 to zero through the use of additionalcoils positioned at right angles to coils 28 and 30 to create anopposite but equal field. It may also be suitable to reduce the localmagnetic field component to zero throughout treatment using additionalcoils or the like.

Referring now to FIG. 4 of the drawings, a block diagram is shown whichdepicts one preferred arrangement of the circuits of cancer treatmentapparatus 20 in functional segments. Numerous other circuit arrangementsmay be possible if the principles of the present invention arefaithfully observed. Microcontroller or microprocessor 100 is seen bywhich the composite magnetic field is maintained at a constantpredetermined level despite changes in the ambient component aspreviously described. In this respect, input 102 is provided by which aset point value of the predetermined composite magnetic flux densityalong a predetermined axis through the target tissue is input intomicroprocessor 100. As will be shown, the composite field strength iscompared to this set point value to generate an error equal to thedifference in the set point value and the measured value of thecomposite magnetic flux density along the axis.

Magnetic field sensor 104 is provided by which the magnitude of thecomposite field which passes through the target tissue along the axis ismeasured. It is preferred that magnetic field sensor 104 comprise aHall-effect or a flux gate device each of which, as will be known bythose skilled in the art, can sense both time-varying and staticmagnetic fields and each produces an analog signal. The magnetic fieldsensor 104 constantly monitors the composite magnetic field, sending asignal to microprocessor 100. It will be understood that the output of aHall-effect or flux gate magnetic sensor is relatively small; thus,magnetic field sensor amplifier 106 is provided by which the signal frommagnetic field sensor 104 is amplified, for example, up to threethousand times its original value. Since these devices produce an analogsignal, analog-to-digital converter 107 is provided by which theamplified signal from magnetic field sensor 104 is converted to adigital signal which can be used by microprocessor 100. It is preferredthat the analog-to-digital converter be provided on-board themicroprocessor chip.

As will be appreciated, the amplification of the magnetic field sensorsignal may produce an unwanted noise level. Also, sudden changes in themagnetic field intensity may occur which make it difficult to determinethe true average value of the composite magnetic flux density. Hence,the signal from analog-to-digital converter 107 which is input intomicroprocessor 100 is filtered by software filter 108 to remove shotnoise and sudden fluctuations in the composite field detected bymagnetic field sensor 104. Although it is preferred that filter 108comprise software in microprocessor 100, a discrete filter could beused. In this embodiment, software filter 108 is a digital filter,preferably an integrator with a time constant of approximately 0.5seconds. In other words, the changes in the magnitude of the compositemagnetic field which are compensated for by increasing or decreasing theapplied field are long-term changes of 0.5 seconds or more. Hence, thetime constant of filter 108 should be such that momentary fluctuationsare filtered out.

Microprocessor 100 includes logic which calculates the non-zero netaverage value of the composite magnetic flux density. This non-zeroaverage value is then compared at a comparator 110 in microprocessor 100to the predetermined dc reference or offset value which is input intomicroprocessor 100 via input 102. It should be noted that this referencevalue is preferably established by dedicated circuitry in microprocessor100, although variable input means could be included by which the setpoint value could be changed. An error statement is then generateddefining the difference in the measured value of the composite magneticflux density and the set point or reference value. Microprocessor 100then determines the magnitude of the output necessary to drive magneticfield generating coils 112 to bring the composite magnetic flux densityback to the set point.

Software field modulator or oscillator 114 is provided by which an ac orfluctuating component is superimposed on the digital output signal whichis input into digital-to-analog converter 116. From the previousdiscussion of the present invention, it will be understood that softwarefield modulator 114 of microprocessor 100 in the preferred embodiment ofthe present invention is preset to a fixed, predetermined frequency toproduce the desired predetermined ratio of frequency-to-magnetic fluxdensity value. In another embodiment, the feedback system of the presentinvention is such that changes in the composite magnetic flux densityare measured, whereupon microprocessor 100 determines the necessarychange in frequency to maintain the predetermined relationship. In thatembodiment, software field analog converter 116 be provided on-board themicroprocessor chip. Hence, software field modulator 114 provides the accomponent at node 118.

The signal from digital-to-analog converter 116 is fed tovoltage-to-current amplifier 120, the output of which drives magneticfield generating coils 112 in the desired manner. Hence, the compositefield is held substantially constant despite changes in the ambientcomponent.

While several arrangements of power sources are suitable, it ispreferred that power supply 122 be provided to power magnetic fieldsensor amplifier 106, microprocessor 100 and magnetic field sensor 104,the latter via bias circuitry 124. A separate power source 126 ispreferred for voltage to current amplifier 120.

Having fully described one preferred embodiment of the apparatus of thepresent invention, including its manner of construction, operation anduse, the method of the present invention will now be described. It is tobe understood that this description of the method incorporates theforegoing discussion of the novel apparatus. In one embodiment, thepresent invention provides a method of reducing the rate of growth of aneoplasm in man or animals. This is achieved in one aspect by generatinga fluctuating, directionally-oriented magnetic field which projectsthrough the cancer cells, for example a malignant neoplasm such as asarcoma, in the presence of a chemotherapeutic agent as previousdescribed. It is to be understood that the present invention may also beuseful in reducing the rate of growth of benign tumors. The magneticfield generating means preferred for use is previously described. Themagnetic field so generated has a magnetic flux density of preciselycontrolled parameters which passes through the target neoplasm parallelto a predetermined axis projecting through the neoplasm. As will beknown by those skilled in the art and as has been clearly explained, thelocal magnetic field to which the neoplasm is subjected will have acomponent which is parallel to the predetermined axis and which thusaids or opposes the applied or generated magnetic field along the axis.At times, the local component may be zero. In the method of the presentinvention, the density of this combined magnetic flux, and morespecifically the net average non-zero value of the combined magneticflux density, is controlled to provide a precise relationship betweenthe flux density along the axis and the frequency of the appliedmagnetic field which is oscillating at a predetermined value. Mostpreferably this is accomplished by adjusting the intensity of theapplied field to compensate for changes in the local field. Thus, in oneembodiment, the present invention provides a method of treating cancerby creating a magnetic field which penetrates a malignant neoplasm andwhich has a predetermined relationship between frequency of oscillationand average flux density. In the most preferred embodiment, thepredetermined relationship or ratio of frequency-to-field intensity isdetermined with reference to the equation:

    f.sub.c /B=q/(2πm)

where f_(c) is the frequency of the combined magnetic field along thepredetermined axis in Hertz, B is the non-zero net average value of themagnetic flux density of the combined magnetic field parallel to theaxis in Tesla and q/m is in Coulombs per kilogram and has a value offrom about 5×10⁵ to about 100×10⁶. B preferably has a value not inexcess of about 1×10⁻² Tesla.

In order to maintain a fluctuating magnetic field having the desiredparameters, it may be necessary to monitor changes in the compositemagnetic field parallel to the predetermined axis. As stated, this ispreferably carried out with a Hall-effect device or the like which iscapable of sensing both static and time-varying magnetic flux and whichproduces an analog signal. This analog signal is periodically sampled bymicroprocessing means which then calculates the necessary frequencyand/or magnitude of the applied magnetic field to maintain thepreprogrammed, predetermined ratio previously described. Of course, itwill now be understood that it is the combined magnetic flux which issensed by the magnetic field sensor. The magnetic field generating meansis used to adjust the magnitude of this composite field whereappropriate.

In one embodiment, the method includes controlling the average value ofthe applied magnetic flux density along a predetermined axis to maintaina predetermined ratio of frequency-to-composite magnetic flux density.In another embodiment, the frequency of the fluctuations is adjusted tomaintain this relationship in which changes in the combined magneticflux density due to changes in the local magnetic field are detected.Moreover, a combination of these two methods may be used wherein boththe frequency and the magnitude of the magnetic field flux density areadjusted to maintain the predetermined relationship of the presentinvention.

Hence, in one aspect the method of the present invention includes thesteps of creating and maintaining a predetermined relationship betweenthe frequency of a fluctuating magnetic field and the flux density ofthe field. In particularly preferred embodiments, a frequency of 16Hertz and an average flux density of 2.09×10⁻⁵ Tesla are utilized whichcorresponds to cyclotron resonance for Ca⁺⁺. This combination offrequency and flux density is particularly useful in decreasing theproliferation rate of cancer cells in the presence of a chemotherapeuticagent. Another preferred frequency which is useful is 16 Hertz and4.07×10⁻⁵ Tesla which corresponds to cyclotron resonance for K⁺.

In a preferred embodiment of the method of the present invention, theratio of frequency-to-flux density is determined by selecting apreselected ion present in the neoplasm and tuning the fluctuatingcomposite magnetic flux density to the specific cyclotron resonancefrequency for the ion. The preferred ions for increasing the inhibitionof cancer cells in the presence of a chemotherapeutic agent are Li⁺, K⁺,Mg⁺⁺, and Ca⁺⁺. Tuning to other ions such as Mn⁺⁺, Zn⁺⁺ or Cu⁺ may alsoprovide beneficial results.

Finally, the subject neoplastic tissue is exposed to the therapeuticmagnetic flux in accordance with the present invention for a period oftime sufficient to bring about the desired result. It is believed thatexposure in accordance with the present invention of approximately 0.5hr. to 24 hr./day will typically provide beneficial results.

In another preferred embodiment of the present invention, the treatmentheads of cancer treatment apparatus 20 contain two discrete butotherwise equal windings. Each head contains a dc winding and an acwinding. These windings are closely wound, either as alternate wires, asalternate layers, or in adjacent planes. Those skilled in the art willrecognize that the closeness of the winding arrangement will ensure thatthe two separate magnetic fields generated at a point distant from thetwo windings (when each carries substantially the same current) will besubstantially the same. The dc winding in one coil is connected inseries aiding to the dc winding in the other coil. The ac winding in onecoil is similarly connected in series aiding to the ac winding in theother coil.

The pair of dc windings are energized by a dc power supply that providesa current which reduces the component of the local or ambient fieldalong the axis of the coil pair at the desired treatment region to avalue that is substantially zero. Again, the ambient field is measuredby magnetic field sensing means such as a Hall device or a fluxgatemagnetometer or the like. The ac windings, in this embodiment, arepreferably energized by a full-wave rectifier circuit providing acurrent which produces a resulting ac magnetic field component along thecoil axis at the desired treatment region that varies in time at thetherapeutic frequency. The rms current of the rectified signal in the accoil pair is adjusted until a preselected rms magnetic field componentat the treatment region is achieved. It will be understood that once theambient field is measured, knowledge of the coil geometry and number ofturns will allow a predetermined calibration, enabling the operator toautomatically achieve the required ambient field nulling current as wellas the rms current necessary to create the preselected rms magneticfield.

In this embodiment utilizing a rectified signal in the ac windings, thefrequency of the fluctuating magnetic field is set at a predeterminedvalue, and the effective or root-mean-square value of the appliedmagnetic flux density is then regulated to produce a ratio of frequencyto flux density that acts to reduce the rate of growth of cancer cells.Preferred ratios of frequency-to-field intensity are determined withreference to the equation: ##EQU2## where f₀ is the frequency of thefluctuating magnetic field in Hertz, B₀ is the non-zero rms value of themagnetic field component winding along the coil axis in Tesla, (q/m) isin Coulombs per kilogram and has a value of from about 5×10⁵ to about100×10⁶. B₀ preferably has a value not in excess of 1×10⁻² Tesla. In oneembodiment, the values of q and m are selected with reference to thecharge and mass of a preselected ion. Other relationships betweenfrequency and magnitude may be useful or even desirable in a particularapplication.

In another embodiment, a sinusoidal current is employed in the acwindings with a direct current offset resulting in a non-zero averagemagnetic field to achieve the required magnetic field along thepredetermined axis that is therapeutically effective.

In still another embodiment, and referring now to FIG. 5 of thedrawings, three pairs of Helmholtz-like coils generate applied magneticfields along the x, y and z axes of a Cartesian coordinate system. Coilpair A comprises treatment heads 200 and 202. Coil pair B comprisestreatment heads 204 and 206, and coil pair C similarly comprises a pairof opposed coils, only one of which is shown in phantom as treatmenthead 208. It will be appreciated that these coils may comprise singlewindings or may be provided in the combination ac and dc windings aspreviously described. Also, it is preferred that each pair be providedwith a magnetic field sensing device in order to measure the magneticfield component along each respective axis. In other words, the axes ofthe three coil pairs will be mutually perpendicular, intersecting at thedesired treatment region, i.e., the target malignant neoplasm. Thetherapeutic frequency is generated by each coil pair in theaforementioned described manner. Where the coil pairs include ac and dcwindings, the ambient field component along each axis is reduced tosubstantially zero.

In still another embodiment of the present invention, the growth rate ofa neoplasm in the presence of a chemotherapeutic agent is reduced bycreating and maintaining a predetermined relationship between thefrequency of the fluctuations and the non-zero average value of themagnetic flux density along the predetermined axis based on thecharge-to-mass ratio of the preselected ion, wherein this predeterminedrelationship is determined using the equation f_(ch) =XBq/2πm.Accordingly, f_(ch) is the frequency of the fluctuating magnetic fluxdensity in Hertz, B is the non-zero average value of the flux densityparallel to the predetermined axis in Tesla, q is the charge of thepreselected ion in Coulombs, m is the mass of the preselected ion inkilograms, and X is a preselected odd integer greater than one. In thismanner, a number of higher harmonic frequencies are provided by whichtherapeutic results may be achieved.

It will be recognized that the fundamental therapeutic frequency f_(c)is effectively multiplied by a selected odd integer to produce afrequency which also causes the desired therapeutic result. Unlessotherwise specified, as used herein, the term "odd integers" or "oddinteger" shall mean positive, non-zero integers. The preferred oddintegers for use in the present invention which provide harmonicfrequencies that should be effective in reducing the growth rate ofcancer are selected from the group consisting of the following integers:three, five, seven, nine, eleven, thirteen, fifteen, seventeen andnineteen. Additional harmonic frequencies based on multiplying thefundamental frequency by an odd integer may also be suitable in someapplications. As indicated, the frequencies for a given preselected ionand known magnetic flux density B can be determined with reference tothe equation f_(ch) =XBq/2πm where f_(ch) is the frequency in Hertz ofthe fluctuating magnetic field along a predetermined axis extendingthrough the target tissue, B is the magnetic flux density along the axisin Tesla, q is the charge of the preselected ion in Coulombs, m is themass of the preselected ion in kilograms, and X is a selected oddinteger greater than one. It is believed that many of the preferred oddmultiple harmonic frequencies will be substantially as effective intreating cancer as are the fundamental frequencies. A more thoroughdescription of harmonic tuning is set forth in the aforementioned U.S.patent application Ser. No. 343,017 which is incorporated herein byreference.

In still another aspect, the present invention provides a method fordecreasing the proliferation rate of cancer cells which comprisesgenerating an applied magnetic field parallel to a predetermined axiswhich projects through the designated space. In the presence of at leasttwo different predetermined ionic species in the target cancer cells ortissue and a chemotherapeutic agent, the neoplasm is exposed to theapplied magnetic field. In one embodiment, the neoplasm is also exposedto a local magnetic field having a component parallel to thepredetermined axis. The magnetic flux density along the predeterminedaxis is fluctuated to create a non-zero average value. Where a localfield is also present, this non-zero average value is the net non-zeroaverage value of the applied and local field components parallel to thepredetermined axis as previously described in connection with the otherembodiments of the present invention.

A predetermined relationship between the frequency of the fluctuationsand the non-zero average value of the magnetic flux density along theaxis is then created and maintained which simultaneously controls themovement of two or more preselected ions. Ion movement is brought aboutto decrease the growth rate of the neoplasm. In one embodiment, thepredetermined relationship is determined by first solving the equationfc=Bq/2πm at a generally randomly selected value of B for each distinctpreselected ion, where f_(c) is the frequency of the field fluctuationsin Hertz, B is the non-zero average value of the flux density parallelto the predetermined axis in Tesla, q is the charge of each preselectedion in Coulombs, and m is the mass of each preselected ion in kilograms.The value of B is preferably less than about 10⁻² T. This establishesthe fundamental cyclotron frequency for each ion. A value f_(cs) ispreferably selected such that none of the individual ion f_(c) valuesdeviate more than 5 percent from the f_(cs) value. In most instances,there will be no f_(cs) value available based on the fundamental f_(c)values of the preselected ions. Accordingly, a higher odd harmonicfrequency of at least one of the preselected ions is determined with theequation f_(ch) =XBq/2πm as previously explained. The values of f_(c)and f_(ch) are examined to determine whether an f_(ch) value can beselected based on a 10 percent and most preferably a 5 percent deviationfactor. If not, the process is continued for each value of f_(ch),beginning with the lowest odd harmonic f_(ch) values until a value off_(cs) can be established within the 5 percent deviation. Hence, at thevalue selected for B during the calculation of the f_(c) or f_(ch)values, the magnetic flux density to which the target tissue is exposedis fluctuated along the axis at the f_(cs) frequency. This specificrelationship between frequency and field strength brings aboutsimultaneous transmembrane movement of the preselected ions fordecreasing the proliferation rate of the target cancer cells.

In more detail, the fundamental frequency at which the fluctuatingmagnetic field would be oscillated for cyclotron resonance regulation oftransmembrane ion movement is calculated individually for each differentionic species to be regulated using the equation f_(c) =Bq/2πm for aselected value of B, which is again the non-zero average value of theflux density along the predetermined axis. As previously explained,f_(c) is in Hertz, q is in Coulombs, m is in kilograms, and q/m is thecharge-to-mass ratio of the preselected ion. Once the fundamentalcyclotron resonance frequency (f_(c)) of each ion to be regulated iscalculated, a regulating frequency (f_(cs)) is determined which ispreferably within 5 percent of the fundamental frequency f_(c) or an oddharmonic frequency f_(ch) of each preselected ion. The odd harmonicfrequencies are determined again using the equation f_(ch) =XBq/2πm,where X is an odd integer greater than one. It will be understood thatthe equation f_(ch) =XBq/2πm can be used to determine the fundamentalfrequency f_(c) by using a value of 1 for X. While the value of f_(cs)will not typically be available which is common to the fundamentalfrequencies and/or odd harmonic frequencies for each preselected ion, ithas been found that an f_(cs) value which is within about 10 percent andpreferably about 5 percent of each f_(c) value or f_(ch) value of theions to be regulated satisfactorily provides simultaneous transmembranemovement of each preselected ion in the field.

It will also be understood that the values of f_(ch) are a function ofB. Thus, it may be possible to obtain an f_(cs) value for a particularset of ions which is within the preferred 5 percent deviation at adesignated B value, but not a higher B value. For use in the presentinvention, the value of B is preferably less than about 1×10⁻² T, with apeak-to-peak amplitude of about 2.0 to about 20,000μ Tesla. Thepreferred ions are those previously set forth. A more thoroughdescription of multiple tuning is set forth in the aforementioned U.S.patent application Ser. No. 343,017 which is incorporated herein byreference.

It will therefore be appreciated that in the broadset sense, the presentinvention provides a method and apparatus for regulating the growthcharacteristics of cancer cells, i. e. treating cancer, by subjectingthe cells to a magnetic environment in which the ratio of the magneticflux density to the frequency of oscillation of a fluctuating fieldcomponent is maintained at a predetermined relationship based on thecyclotron resonance frequency of at least one ion in the field. Thisrelationship may be selected to decrease the proliferation rate ofcancer cells exposed to a particular chemotherapeutic agent or selectedto increase the differentiation of of cancer cell neurites to inhibitmalignancy. It may be possible to select a relationship which decreasesthe rate at which cancer cell proliferation occurs even without the useof a chemotherapeutic agent. In its most preferred embodiments, thepresent invention provides a method and apparatus which includes tuningto the cyclotron resonant frequency of Ca⁺⁺ or K⁺ or a selected multipleof these frequencies in the presence of a chemotherapeutic agent todecrease proliferation rate. In another most preferred aspect, thepredetermined relationship is based on multiple harmonic tuning for bothCa⁺⁺ and Mg⁺⁺ in the presence of a chemotherapeutic agent where therelationship represents three times the fundamental frequency of thecalcium ion and five times the fundamental frequency of the magnesiumion. In the latter case, it is the formation of neurites which isstimulated.

In still another aspect the present invention provides an apparatus forthe systemic therapeutic treatment of cancer. By "systemic treatment" itis meant that substantially all of the subject's body is simultaneouslyexposed to the therapeutic magnetic fields in accordance with thepresent invention. Accordingly, and referring now to FIG. 6 of thedrawings, systemic treatment apparatus 280 is shown which comprises atube or cylinder 282 of a non-magnetic material such as plastic. Tube282 houses a large solenoid 284 which contains multiple turns of wire286 and which extends substantially the entire length of systemictreatment apparatus 280. Gurney or platform 288 is provided on a tracksystem (not shown) which allows platform 288 to move between a firstposition outside of tube 282 to a second position inside of tube 282. Acontroller 270 is provided along with the necessary circuitry forenergizing solenoid 284 to create a magnetic field in the direction ofaxis 250, which in this embodiment projects through the central bore ofsolenoid 284. In other words, and as will be appreciated by thoseskilled in the art, the magnetic flux generated by solenoid 284 will runthrough the center of the coil. Patient 272 is placed on a platform 288and platform 288 is then moved into position inside tube 282. Thuspatient 272 is positioned inside solenoid 284 with the applied magneticflux penetrating the patient's entire body in the direction ofpredetermined axis 250. In one embodiment a magnetic field sensor 274 isalso provided to measure the magnetic flux density along axis 250 andmay be mounted on a track system within tube 282. It may be suitable insome applications to mount tube 282 on a rotatable stand such that tube282 can be rotated to change the position of patient 272 and axis 250with respect to the local magnetic field. Other configurations ofsystemic treatment apparatus 280 may be suitable or even desirable in aparticular application such as large flat coils (for example havingdiameters of six feet or greater) in Helmholtz arrangement with one coilbeing placed on each side of patient 272. In this alternativearrangement, axis 250 would extend transverse to the patient's bodyrather than from toe-to-head as shown in FIG. 6. Of course, thedirection of the magnetic field may also be directly opposite to thedirection of axis 250 depending upon the direction of current throughsolenoid 284. Systemic treatment apparatus 280 is thus used to create amagnetic field of predetermined parameters inside tube 282. While thispredetermined relationship is preferably maintained by adjusting theapplied flux to compensate for changes in the local field component;alternatively, the frequency can be adjusted to preserve the desiredratio.

For systemic treatment, a patient 272 afflicted with cancer is placed onplatform 288 which is then moved into position within tube 282 and thuswithin solenoid 284. Patient 272 is then subjected to a fluctuatingmagnetic field of the nature previously described for a period of timesufficient to bring about the desired systemic treatment. It is believedthat exposure in accordance with the systemic treatment embodiment ofthe present invention of about 0.5 hr. to 24 hr./day until the desiredresult is achieved.

Referring now to FIG. 7, a block diagram is shown which is preferred foruse in connection with the systemic treatment apparatus 280. Operatingconsole 320 forms the control center for operating systemic treatmentapparatus 280. The console is comprised of a plurality of controlelements 322 and a visual display device 324 for monitoring the waveform display of the solenoid current signal 325. The plurality ofcontrol elements 322 include a gurney positioning dial 326 forcontrolling the lateral movement of the gurney platform. Magnetic fieldsensor adjusting dial 328 allows the operator to selectively positionthe magnetic field sensor 327 within the center of treatment solenoid284. The treatment structure rotating dial 330 allows the operator torotate the concentric solenoid and platform 288 in the horizontal planein that embodiment where a supporting stand or turntable (not shown) isprovided. This horizontal movement allows the solenoid coil to bepositioned so that it may compensate for undesired local magneticfields. Switch elements 332 allow the operator to effect various othercontrol tasks, such as turning the concentric solenoid current on oroff, or setting the cyclotron resonance frequency for the ion of choice.Each of the above-mentioned dials and switch elements produce signalswhich go to various elements of system treatment apparatus 280 toaccomplish the various functions described herein. The signal producedby the gurney positioning dial 326 leaves operating console 320 alongcable 334 as does the signal produced by the treatment structurerotating dial 330. The signals 334 interface with various motors andother drive hardware to effect the positioning of platform 288 withinsolenoid 284 and the positioning of tube 282 with respect to the localmagnetic field. Control line 336 transmits the signal developed by themagnetic field sensor adjusting dial 328 to a magnetic sensorpositioning device 338 which allows the magnetic sensor 327 to bepositioned at various locations within the center of the solenoid 284.After dials 326 through 330 and switches 332 have been set, systemictreatment apparatus 280 is ready for operation. The frequency which hasbeen selected by the operator is output along line 340 to the sine wavegenerator 342. The sine wave generator 342 responds to the frequencyselected in accordance with the principles of the present invention bygenerating a sinusoidal waveform which possesses one-half of the desiredfrequency with no DC offset. The signal is then sent from the sine wavegenerator 342 to a full-wave rectifier circuit 346. Rectifier 346 notonly transforms the sinusoidal waveform produced by generator 342 to arectified DC signal, it also has the effect of doubling the frequency ofthe output of the sine wave generator. The rectified signal is then sentfrom the full-wave rectifier 346 to the programmable power supply 348where it is amplified to a sufficient power level which is necessary todevelop a sufficiently strong magnetic field within the solenoid 284.The amplified signal is then sent from the programmable power supply 348along cable 350 to solenoid 284. Solenoid 284 then converts theamplified current to a uniform magnetic field density within theconcentric solenoid winding 284 along axis 250 shown in FIG. 6. Becauseof localized magnetic fields, the magnetic field, as it exists withinthe concentric solenoid winding, is not always absolutely predictable.Thus, magnetic sensor 327 is mounted in close proximity to the patientso that the magnetic flux density within solenoid 284 can be constantlymonitored. A signal, which is proportional to the magnetic flux densitywithin treatment solenoid 284, is output by the magnetic sensor 327 andthen filtered by filter 331 to eliminate any undesired high-frequencyelements. The output of low-frequency filter 331 is then delivered tooperating console 320 along cable 333 so that it can be displayed on thevisual display device 324. The output of low-frequency filter 331 isalso sent to analog amplifier 335 so that it can be properly conditionedto be used within the programmable power supply 348. The programmablepower supply 348 uses the output from analog amplifier 335 as a meansfor maintaining a uniform density magnetic field within the center ofsolenoid 284. This task may be performed within the programmable powersupply by means of standard analog feedback techniques or may beaccomplished by means of a digital processor.

The following examples are provided to more fully illustrate the presentinvention and are not intended to limit the scope of the invention asdefined in the appended claims.

EXAMPLE I

N-18 neuroblastoma tumor cells from the American Type Culture Collection(ATCC) were cultured in Linbro 12-well culture plates in either I-10 orI-H media, at 37° C., with 5% CO₂ in air at 100% humidity. The formulaefor the media is as follows:

    ______________________________________                                        I-10                                                                          Dulbecco's Minimum Essential Medium                                                                          50     ml                                      (double strength)                                                             Fetal Calf Serum               10     ml                                      20% Glucose solution           3      ml                                      L-Glutamine (200 mM solution)  1      ml                                      Penicillin/Streptomycin (Gibco Prepared)                                                                     1      ml                                      H.sub.2 O               q.s.   100    ml                                      I-H                                                                           DMEM (2X)                      50     ml                                      Horse Serum                    25     ml                                      20% Glucose                    3      ml                                      L-Glutamine                    1      ml                                      Penicillin/Streptomycin (Gibco Prepared)                                                                     1      ml                                      H.sub.2 O               q.s.   100    ml                                      ______________________________________                                    

50% of the cultures received ARA-C (Cytosine Arabinoside) at a finalconcentration of 0.25 micrograms/ml, an inhibitor of neuroblastomagrowth. Experimental cultures also received 24 hours combined magneticfield stimulation adjusted to ion cyclotron resonance values for Ca⁺⁺ orK⁺ according to the method and formula of the present invention.Treatment was accomplished by placing the culture dishes in the spacebetween the energized Helmholtz-aiding coils in the incubator so thatthe combined magnetic fields passed through the culture medium and cellsparallel to the surface of the medium and the bottom of the dish. Thefollowing protocol was used:

    ______________________________________                                        Culture    ARA-C      CR Ion   No. or Cultures                                ______________________________________                                        Control I-10                                                                             Yes        none     9                                              Control I-H                                                                              Yes        none     9                                              Control I-10                                                                             No         none     9                                              Control I-H                                                                              No         none     9                                              I-10       Yes        Ca       9                                              I-10       No         Ca       9                                              I-H        Yes        Ca       9                                              I-H        No         Ca       9                                              I-10       Yes        K        9                                              I-10       No         K        9                                              I-H        Yes        K        9                                              I-H        No         K        9                                              ______________________________________                                    

The medium in each culture dish was renewed every other day. After 3days of culture, the dishes were removed from the incubator, and thecell proliferation rate was established by making cell counts in eachdish. The cells having recognizable neurites (outgrowths at least twiceas long as the cell diameter) were also counted. The data are expressedas number of cells per dish and percent of cells having neurites.

    ______________________________________                                        RESULTS                                                                                    No. Cells/                                                       Category     Dish      p vs C  % Neurites                                                                            p vs C                                 ______________________________________                                        C + ARA-C (I-10)                                                                           37.50     --      16.87   --                                     C + ARA-C (I-H)                                                                            15.78     --      9.29    --                                     C NO ARA-C(I-10)                                                                           66.78     --      12.71   --                                     C NO ARA-C (I-H)                                                                           46.67     --      20.64   --                                     Ca + ARA-C (1-10)                                                                          46.34     .10     9.92    .05                                    Ca + ARA-C (I-H)                                                                           30.78     .01     14.45   .10                                    Ca NO ARA-C (I-10)                                                                         64.72     N.S.    11.59   N.S.                                   Ca NO ARA-C (I-H)                                                                          33.33     .10     22.08   N.S.                                   K + ARA-C (I-10)                                                                           46.56     .10     12.44   N.S.                                   K + ARA-C (I-H)                                                                            20.44     N.S.    12.75   N.S.                                   K No ARA-C (I-10)                                                                          68.00     N.S.    12.57   N.S.                                   K No ARA-C (I-H)                                                                           24.00     .01     20.93   N.S.                                   ______________________________________                                    

These results indicate that CR fields can influence the growth of tumorsin vitro and can alter the effects of an antitumor drug on the cells.The tuning for Ca⁺⁺ and K⁺ had little effect on the outgrowth ofneurites. The tuning for Ca had some effect, depressing outgrowthstrongly in I-10, which contains strong fetal growth factors andenhancing growth slightly in I-H, which lacks the growth factors ofI-10.

Neither Ca⁺⁺ nor K⁺ tuning overcame the strong effect of cellproliferation factors contained in I-10 medium as a result of theincorporation of the fetal calf serum. The effect was essentially null,even in the presence of ARA-C. However, when I-H was used, which is morenearly similar to normal adult serum by virtue of the absence of thefetal cell proliferation factors, the CR tuning for Ca produced anincrease in cell proliferation, partly overcoming the inhibitory effectof the ARA-C.

When K⁺ tuning was used in I-H medium, in the presence of ARA-C, therewas essentially no effect, the ARA-C being a strong inhibitornotwithstanding.

In the absence of the ARA-C, using the I-H medium, Calcium tuningproduced a slight depression of cell proliferation.

When K tuning was used in the absence of ARA-C in I-H medium, there wasa very strong suppression of cell proliferation. In fact, thesuppression produced by the K⁺ signal was statistically equivalent tothe effect of the potent pharmacological agent, suggesting that undersome circumstances, the use of cyclotron resonance may be as effective atreatment modality as a standard pharmacological agent, but perhapswithout the negative side effects of the pharmacological agent.

EXAMPLE II

In this example the medium was identical to I-10 above, except the serumconcentration was reduced to 2.0 ml. In the following table, thereduction in proliferation achieved by the present invention is againdemonstrated with respect to the synergistic effect of cyclotronresonance treatment in the presence of chemotherapeutic cancer agents.The experiments were conducted for 72-hour periods. The cells were N-18neuroblastoma cells.

K=potassium ion (K⁺)

Ca=calcium ion (Ca⁺⁺)

H=Mg/Ca 3/5 harmonic tuning

C-=control plates without ARA-C and without cyclotron resonance exposure

C+=control plates with ARA-C and without cyclotron resonance exposure

E-=experimental plates without ARA-C and with cyclotron resonanceexposure

E+=experimental plates with ARA-C and with cyclotron resonance exposure

0.5=1/2 hour field exposure per 24 hours

24=continuous field exposure (ARA-C=cytosine arabinoside [conc. 0.25micrograms/ml]) (cell processes refers to neurites)

    __________________________________________________________________________    TOTAL CELLS/MM.sup.2 +- S.D.                                                  ION/TIME                                                                             C-      C +     E-      E+                                             __________________________________________________________________________    K/.5 H  47.8-27.4                                                                            28.5-14.9                                                                             215.1-124.2                                                                           43.6-22.9                                      K/24 H  81.9-59.0                                                                            34.1-19.3                                                                             218.7-95.8                                                                            50.3-28.0                                      Ca/.5 H                                                                               33.3-15.0                                                                            18.6-9.0                                                                              129.3-44.2                                                                            26.2-17.2                                      H/.5 H 142.9-55.1                                                                            33.3-22.0                                                                             167.0-60.4                                                                            26.3-11.1                                      Mg/.5 H                                                                               36.5-40.5                                                                            11.7-9.8                                                                               51.7-34.8                                                                            10.7-7.8                                       (H = Mg/Ca, 3/5 Harmonic Tuning)                                              % CELLS WITH PROCESSES +- S.D.                                                K/.5 H 10.8-6.3                                                                              13.8-8.9                                                                              11.1-6.8                                                                              10.0-7.5                                       K/24 H  9.0-4.6                                                                               7.2-7.6                                                                               7.3-3.2                                                                               4.2-3.7                                       Ca/.5 H                                                                              12.9-6.8                                                                              19.4-11.9                                                                             17.2-6.3                                                                              14.6-10.9                                      H/.5 H 21.2-6.6                                                                              12.9-8.7                                                                              20.1-5.9                                                                              15.2-7.6                                       Mg /.5 H                                                                              9.9-6.9                                                                               6.3-11.2                                                                              8.6-5.2                                                                               3.8-7.7                                       __________________________________________________________________________    STATISTICAL COMPARISONS, TOTAL CELLS                                          (t, (p))                                                                             C- vs C+                                                                               E- vs E+                                                                             C- vs E-                                                                              C+ vs E+                                       __________________________________________________________________________    K/.5 H  3.67 (<.001)                                                                          8.03 (<.001)                                                                          7.89 (<.001)                                                                         3.35 (<.005)                                   K/24 H  4.56 (<.001)                                                                          9.98 (<.001)                                                                          7.29 (<.001)                                                                         2.85 (<.01)                                    Ca/.5 H                                                                               5.08 (<.001)                                                                         13.06 (<.001)                                                                         12.35 (<.001)                                                                         2.36 (<.05)                                    H/.5 H 11.09 (<.001)                                                                         13.75 (<.001)                                                                          1.78 (N.S.)                                                                          1.72 (N.S.)                                    Mg/.5 H                                                                               3.56 (<.005)                                                                          6.99 (<.001)                                                                          1.72 (N.S.)                                                                          0.54 (N.S.)                                    __________________________________________________________________________    % CELLS WITH PROCESSES                                                        (t, (p))                                                                      K/.5 H 1.63 (N.S.)                                                                           0.65 (N.S.)                                                                           0.19 (N.S.)                                                                           1.96 (=.05)                                    K/24 H 1.20 (N.S.)                                                                           3.75 (<.001)                                                                          1.88 (N.S.)                                                                           2.11 (<.05)                                    Ca/.5 H                                                                              2.86 (<.01)                                                                           1.26 (N.S.)                                                                           2.81 (<.01)                                                                           1.80 (N.S.)                                    H/.5 H 4.56 (<.001)                                                                          3.05 (<.01)                                                                           0.77 (H.S.)                                                                           1.18 (N.S.)                                    Mg/.5 H                                                                              1.04 (N.S.)                                                                           3.09 (<.005)                                                                          0.43 (N.S.)                                                                           1.04 (N.S.)                                    n for all experiments = 36                                                    __________________________________________________________________________

Thus, it is apparent that there has been provided in accordance with theinvention a method and apparatus that fully satisfies the objects, aimsand advantages set forth above. While the invention has been describedin connection with specific embodiments thereof, it is evident that manyalternatives, modifications, and variations will be apparent to thoseskilled in the art in light of the foregoing description. For example,it is to be understood that higher harmonic tuning and multiple iontuning as described herein may be useful in connection with thecontemporaneous use of chemotherapeutic cancer agents. Accordingly, itis intended to embrace all such alternatives, modifications andvariations that fall within the spirit and broad scope of the appendedclaims.

What is claimed is:
 1. A method of treating cancer comprising of stepsof:(1) determining a desired composite magnetic flux having a staticfield component for treatment of a cancer; (2) placing a patientafflicted with cancer inside a container, and associated magnetic fieldgenerator; (3) applying a fluctuating magnetic flux to the patient inwith said associated magnetic field generator along an axis; (4) sensingthe actual composite magnetic flux along the axis in the patient,wherein the actual composite magnetic flux includes a component of thefluctuating applied magnetic flux and a component of the naturallyexisting static magnetic flux; and (5) comparing the actual compositemagnetic flux to the desired composite magnetic flux, determining anerror value, and modifying the applied magnetic flux to correct theerror value.
 2. A method as recited in claim 1, wherein a microprocessorstores the desired values of step (1), the microprocessor also beingutilized to perform the functions of step (5), including comparing theactual and desired composite magnetic flux values and determining theerror value, the microprocessor also generating a signal to be sent to apower source for the applied magnetic flux to correct the error value.